Highly Stereoselective α-Hydroxyalkylation/Chlorination of α,β-Acetylenic Ketones—An Efficient Approach to β-Halogeno Baylis–Hillman Adducts

A highly stereoselective method for the synthesis of (E)-β-halogeno Baylis–Hillman adducts has been developed. The new method involves a tandem α-hydroxyalkylation/β-chlorination of α,β-acetylenic ketones by using TiCl4 as the chlorine source for α,β-conjugate addition, and concurrently as the Lewis acid promoter for the carbonyl addition. The new system tolerates a broad scope of reactants in which aliphatic and aromatic α-acetylenic ketones can be subjected to the conjugate addition. Both aliphatic and aromatic aldehydes can also be employed as electrophilic acceptors. Good yields (61–88%) and high E/Z stereoselectivity have been obtained for the nine examples which were examined, only in one case was E/Z selectivity of 17/1 observed and the two individual isomers are separable via flash column chromatography.